Khalifa Mohamed, Hmed Ahmed A, Elfeky Khaled S, Bakry Sayed, Hamshary Manal El, Sofy Ahmed R
Zoology Department, Faculty of Science, Al-Azhar University, Nasr City, Cairo 11884, Egypt; Molecular Pathology Laboratory, Children Cancer Hospital, 57357 Cairo, Egypt.
Botany and Microbiology Department, Faculty of Science, Al-Azhar University, Nasr City, Cairo 11884, Egypt.
J Genet Eng Biotechnol. 2025 Sep;23(3):100533. doi: 10.1016/j.jgeb.2025.100533. Epub 2025 Jul 17.
Malignant liver disease is among the highest in the world, with hepatocellular carcinoma (HCC) accounting for up to 90 % of all cases. In Egypt, HCC poses a significant public-health concern, representing 47.17 % of cancer cases. The high incidence of hepatitis C virus (HCV) in the Egypt was a major predisposing factor for HCC.
This study included 63 Egyptian HCC patients, 55 % of whom had a history of HCV infection.
Using a paired sampling strategy, approximately 2800 COSMIC mutations from 50 oncogenes and tumor-suppressor genes were NGS sequenced.
Total of 381 somatic mutations were identified, 91 mutations detected in the HCC group and 291 in the HCV-related HCC group. The top 10 mutated genes in the non-HCV group were TP53, ATM, EGFR, CDH1, FGFR1, MET, SMAD4, ERBB2, FLT3, and FBXW7, while in the HCV-related HCC group, genes were KIT, ATM, TP53, APC, FBXW7, KDR, RB1, SMAD4, EGFR, and PIK3CA.
The present study represents the first comprehensive somatic mutation profile in HCC Egyptian patients. This finding suggests that HCV viral infection played a direct and indirect role in increasing the somatic mutation burden in HCV-related HCC patients and opens new promises of targeted therapies for those patients.
恶性肝病在全球范围内发病率极高，其中肝细胞癌（HCC）占所有病例的90%。在埃及，HCC是一个重大的公共卫生问题，占癌症病例的47.17%。埃及丙型肝炎病毒（HCV）的高发病率是HCC的主要诱发因素。
本研究纳入了63例埃及HCC患者，其中55%有HCV感染史。
采用配对抽样策略，对50个癌基因和肿瘤抑制基因中的约2800个COSMIC突变进行二代测序。
共鉴定出381个体细胞突变，HCC组检测到91个突变，HCV相关HCC组检测到291个突变。非HCV组中前10个突变基因是TP53、ATM、EGFR、CDH1、FGFR1、MET、SMAD4、ERBB2、FLT3和FBXW7，而在HCV相关HCC组中，基因是KIT、ATM、TP53、APC、FBXW7、KDR、RB1、SMAD4、EGFR和PIK3CA。
本研究首次展示了埃及HCC患者全面的体细胞突变谱。这一发现表明，HCV病毒感染在增加HCV相关HCC患者的体细胞突变负担方面发挥了直接和间接作用，并为这些患者的靶向治疗带来了新的希望。
